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A neg OB with anti-Yta


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We have recently identified (with reference lab confirmation) an anti-Yta in an A neg pregnant woman.  She has had one prior pregnancy--miscarriage-- and no transfusions.  We are 3.5 hours from our blood supplier (over a mountain pass) in good weather and she is due about Christmas.  We are convinced that the risk of HDFN is nil so I am devising a plan for managing the patient if she should bleed during delivery.  We can have the MMA done for significance but it is expensive and maybe not worth it when the patient isn't all that likely to bleed excessively.  I am about ready to decide that we should just wing it because I can't get in compatible units "just in case" because they probably would have to be deglycerolized and thus would have a 24 hr expiration.  If she massively hemorrhages, I won't have any choice but to give her Yta untested units.  If she doesn't have a life-threatening bleed there might be time to get in Yta negative blood in a day or 2 to fill her back up.  Autologous donation would give us only maybe 1 liquid unit and they probably would want to transfuse it even if she didn't need it.  Not sure if there is a family member but they can only donate every 56 days and I would want a liquid unit for the month around her due date.  Maybe a sibling could donate a double red cell but that's about the best it will get (assuming there is a Yta neg sibling).  We would try to send out an antibody workup in the last 2 weeks before her due date just to make sure there aren't any new antibodies that we will want to honor.  Of course she will have RhIG on board by then I'm sure.  I will happily take all suggestions and input.

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2 hours ago, Mabel Adams said:

We have recently identified (with reference lab confirmation) an anti-Yta in an A neg pregnant woman.  She has had one prior pregnancy--miscarriage-- and no transfusions.  We are 3.5 hours from our blood supplier (over a mountain pass) in good weather and she is due about Christmas.  We are convinced that the risk of HDFN is nil so I am devising a plan for managing the patient if she should bleed during delivery.  We can have the MMA done for significance but it is expensive and maybe not worth it when the patient isn't all that likely to bleed excessively.  I am about ready to decide that we should just wing it because I can't get in compatible units "just in case" because they probably would have to be deglycerolized and thus would have a 24 hr expiration.  If she massively hemorrhages, I won't have any choice but to give her Yta untested units.  If she doesn't have a life-threatening bleed there might be time to get in Yta negative blood in a day or 2 to fill her back up.  Autologous donation would give us only maybe 1 liquid unit and they probably would want to transfuse it even if she didn't need it.  Not sure if there is a family member but they can only donate every 56 days and I would want a liquid unit for the month around her due date.  Maybe a sibling could donate a double red cell but that's about the best it will get (assuming there is a Yta neg sibling).  We would try to send out an antibody workup in the last 2 weeks before her due date just to make sure there aren't any new antibodies that we will want to honor.  Of course she will have RhIG on board by then I'm sure.  I will happily take all suggestions and input.

It seems to me that you have covered all bases Mabel.

There is a telling sentence in Reid ME, Lomas-Francis C, Olsson ML.  The Blood Group Antigen FactsBook.  3rd edition, 2012, Academic Press (page 419), which states, "Experts agree that anti-Yta are often benign and antigen-negative blood may not need to be transfused."

Certainly in the cases I have seen over the years, I have never had to give Yt(a-) typed blood (although, because of the geography of England (it's a lot smaller than the USA!), such blood could easily be obtained from the National Frozen Blood Bank, and/or from "tame" donors.

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7 hours ago, Mabel Adams said:

We have recently identified (with reference lab confirmation) an anti-Yta in an A neg pregnant woman.  She has had one prior pregnancy--miscarriage-- and no transfusions.  We are 3.5 hours from our blood supplier (over a mountain pass) in good weather and she is due about Christmas.  We are convinced that the risk of HDFN is nil so I am devising a plan for managing the patient if she should bleed during delivery.  We can have the MMA done for significance but it is expensive and maybe not worth it when the patient isn't all that likely to bleed excessively.  I am about ready to decide that we should just wing it because I can't get in compatible units "just in case" because they probably would have to be deglycerolized and thus would have a 24 hr expiration.  If she massively hemorrhages, I won't have any choice but to give her Yta untested units.  If she doesn't have a life-threatening bleed there might be time to get in Yta negative blood in a day or 2 to fill her back up.  Autologous donation would give us only maybe 1 liquid unit and they probably would want to transfuse it even if she didn't need it.  Not sure if there is a family member but they can only donate every 56 days and I would want a liquid unit for the month around her due date.  Maybe a sibling could donate a double red cell but that's about the best it will get (assuming there is a Yta neg sibling).  We would try to send out an antibody workup in the last 2 weeks before her due date just to make sure there aren't any new antibodies that we will want to honor.  Of course she will have RhIG on board by then I'm sure.  I will happily take all suggestions and input.

I echo Malcolm's sentiments - you appear to in control of the situation. One wrinkle, perhaps: Are you able to "sell it" to the physicians ?

It has been many moons, but I have performed dozens of MMAs on examples of anti-Yta. Almost all were considered insignificant and even those that were over the threshold were barely above. Add the fact that they are almost universally IgG4 - no harm to the baby and minimal risk of a transfusion reaction. The examples that did just make it into the "significant" interpretation usually had a touch of IgG1 and/or IgG3. I have no hard data to support it, but I'm quite sure that many of the patients (even those with "significant" results) received Yt(a+) blood without consequence.

If the case arises and in my opinion, giving Rh-negative blood is way more important than fussing about anti-Yta.

Given your geography, it might wise, albeit extremely cautious, to suggest the patient move to the "big city" (Portland) for Christmas, but that would only hold true if the physicians want easier access to Yt(a-) blood.

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If she requires transfusion, should we make an effort to match her for K, C, E, Jkb etc.?  Can we assume that she is a "responder"?  If she makes another antibody it will be very hard to figure out what she has quickly (and locally) in the presence of that anti-Yta.  She's young.  Matching K, C & E would be easy, the Jkb a bit less so, especially among Rh neg units.  Is the anti-Yta likely to remain detectable for decades?

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1.  Personally, I would only go as far as matching her for D, C, c, E, e and K.  These are really the most immunogenic of the more common antigens.

2.  Yes, you can, but that doesn't mean that she will suddenly sprout different antibody specificities like a mint plant sprouts leaves!

3.  Although I have seen quite a few cases of anti-Yta in my time, I have never had to follow one for ant length of time, so I honestly don't know.

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1 hour ago, Mabel Adams said:

If she requires transfusion, should we make an effort to match her for K, C, E, Jkb etc.?  Can we assume that she is a "responder"?  If she makes another antibody it will be very hard to figure out what she has quickly (and locally) in the presence of that anti-Yta.  She's young.  Matching K, C & E would be easy, the Jkb a bit less so, especially among Rh neg units.  Is the anti-Yta likely to remain detectable for decades?

I think matching Rh and K is a good idea. My foggier-by-the-day memory leads me to believe that most of the examples of anti-Yta that I've seen were single specificity. I do remember a couple with anti-D and at least one with anti-c.

As to longevity......anti-Yta tends to fade away over time in the absence of additional stimulation. In your patient, additional pregnancies may be a source of re-stimulation, so her antibody might be more persistent.

As usual, these are generalized statements and opinions. There are always antibodies that don't read the literature.

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2 hours ago, Mabel Adams said:

Since this antibody doesn't cause HDFN due to the antigen not being well-developed in the fetus, why should a miscarriage have sensitized her?  Are they ever naturally occurring?  If so, does that correlate to significance?

The thing is, an antibody specificity may not be clinically significant, but that does not mean that its titre or avidity is not affected by further stimulation.  As exlimey said earlier, the majority of anti-Yta antibodies are IgG4, and IgG4 antibodies never cause haemolytic transfusion reactions, but that does not mean that further stimulation by Yt(a+) red cells will not have an affect on the titre and avidity of this IgG4, or that the further stimulation will suddenly cause the antibody to switch IgG subgroup (although I also acknowledge that exlimey does talk about elements of IgG1 in the stronger examples of the specificity).  Are they ever naturally occurring examples of anti-Yta?  Again, to answer you honestly, I don't know.

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19 hours ago, Mabel Adams said:

Since this antibody doesn't cause HDFN due to the antigen not being well-developed in the fetus, why should a miscarriage have sensitized her?  Are they ever naturally occurring?  If so, does that correlate to significance?

As I understand it, IgG2 and IgG4 do not cross the placenta easily, whereas IgG1 and IgG3 are "actively" transported from Mother to baby. Obviously the baby benefits from this passive immunity. Since most examples of anti-Yta are predominantly IgG4, that's why they don't cause HFDN, especially since, as you mentioned, the Yta antigens are poorly expressed in utero.

Never say never, but I doubt that anti-Yta occurs naturally. Cartwright system antigens are poor immunogens, so from my point of view, the antibody's existence implies repeated stimulation. That being said, your patient may be a "super-responder". I don't if anyone really understands why immune responses vary or how some result in different IgG subclasses.

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Daniels says, "Of those anti-Yta sera that could be subclassed, most contained IgG1, some IgG1 plus IgG4, and a few IgG4 alone; none contained IgG3. Some anti-Yta bind complement, others do not."  He also includes results of testing fetal antigen strength (< 32 weeks gestation) and found 8 of 10 did not react with anti-Yta but 2 did, albeit very weakly.  Interesting stuff.  Thanks so much for sharing your experience with these.

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Incidentally, just to complicate things further, YT03 (YTEG), a novel high prevalence antigen within the YT Blood Group System was ratified at the recent ISBT Meeting in Copenhagen (as was RH62 [CEWA], a novel high prevalence antigen within the Rh Blood Group System).

Just when you think you've learned everything, something else comes along!!!!!!!!!!!!!!!!!!!!!!!!!!!!

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Oddly enough, Wisconsin seems to have lots of Yta neg donors.  We had a patient a few years ago, and Community Blood Center of Appleton Wisc was able to supply us many liquid units. AABB members can use the National Blood Exchange to facilitate this.  So if you do decide to have blood on hand for 4-6 weeks, give them a call.

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Yes, we also have over 30 Yt(a-) donors that we can call upon when we may need them.

If you have a decent anti-Yta available, and a goodly number of donors, when you screen for them, Yt(a-) donors are surprisingly common at just under 1%.  For example, if you have 1000 donors, you will, potentially, detect about nine Yt(a-) individuals.  Doing this by genotyping is swifter and, probably, more cost effective.

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5 hours ago, kate murphy said:

Oddly enough, Wisconsin seems to have lots of Yta neg donors.  We had a patient a few years ago, and Community Blood Center of Appleton Wisc was able to supply us many liquid units. AABB members can use the National Blood Exchange to facilitate this.  So if you do decide to have blood on hand for 4-6 weeks, give them a call.

 

5 hours ago, Malcolm Needs said:

Yes, we also have over 30 Yt(a-) donors that we can call upon when we may need them.

If you have a decent anti-Yta available, and a goodly number of donors, when you screen for them, Yt(a-) donors are surprisingly common at just under 1%.  For example, if you have 1000 donors, you will, potentially, detect about nine Yt(a-) individuals.  Doing this by genotyping is swifter and, probably, more cost effective.

Don't forget....in this case......Rh-negative units are required. Multiply by 0.15 !!!

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2 hours ago, exlimey said:

 

Don't forget....in this case......Rh-negative units are required. Multiply by 0.15 !!!

Well, I agree exlimey, but if they are really worried about exsanguination, AND they are worried about the anti-Yta, then they can give either D Negative units that are Yt(a) untested, or Yt(a-) blood that is D Positive.  That is a clinical decision, but, there will be VERY few centres that supply blood to hospitals who only have 1000 donors, so multiply up the numbers by the number of donors available to the centre.  The 1000 was only a number plucked from the sky!

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  • 2 weeks later...

I offer the following based on experience with the MMA and antibodies to antigens of high prevalence and should not be taken as clinical recommendations.

The National Reference Laboratory for Blood Group Serology for the American Red Cross has performed Monocyte Monolayer Assays (MMAs) in over 200 cases of patients with anti-Yta in order to determine which patients have antibodies of potential clinical significance. The MMA has been performed for more than 30 years. The reason to perform the MMA is to conserve the supply of Yt(a-) units for patients who have had either had decreased survival of transfused RBCs or who have a positive MMA. But the MMA is only useful for determination of transfusion recommendations for the mother, the MMA for prediction of Hemolytic Disease of the Fetus and Newborn has not been found to be useful in studies performed in George Garratty's Research Laboratory in Los Angeles.

For cases like these, an MMA is recommended if blood is thought to be needed for the mother at delivery. Then if a physician determines that the mother can donate autologous units that would be useful. In some cases, 3 different donations can be made with the first two being frozen, one into two aliquots for possible use by the infant and one as a whole unit for the mother's possible use. The final unit can be drawn in order that it will be in-date at the time of the planned delivery. Autologous units do not generally have to follow the same rules as allogeneic donation, and can allow for more frequent donation and at a lower hemoglobin in accordance with the physician order. Alternatively or in addition, a request can be placed by an American Rare Donor Program member for potential units for delivery if autologous units cannot be obtained. And, after delivery, when the woman is eligible for donation, she should be encouraged to donate, not only for herself, but for others. Her siblings should also be tested as they have a 1:4 chance of being Yt(a-).

It is assumed that pregnancies like these are monitored by non-invasive means. Most often, antibodies such as anti-Yta, seldom clinically significant for HDFN, are monitored by titer, reviewing for increases in titer (although not mentioned), and then, by clinical protocol. Opinions vary on critical titer value in non-D antibodies, but most agree that increases in titer are reviewed for further studies or early delivery.

Perhaps not especially needed in this case, but in cases of antibodies to high prevalence antigens, knowledge of the father's ABO and D status, especially prediction of zygosity of the father's D type might be useful in the very rare event of HDFN because O D negative Yt(a-) blood may be challenging.

Sandra Nance, MS, MT(ASCP)SBB, Senior Director, American Rare Donor Program

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